The primary aim of this project is a better understanding of the process of neurosecretion. The neurosecretory process will be investigated in the hypothalamo-neurohypophysial system, whose main function is the release of the neurohormones oxytocin and vasopressin. These neurohormones are released following adequate stimulation, primarily via the central nervous system and represent a major means of control of organismal functions by the nervous system. In the project, neurosecretory granules will be isolated and studied directly. Previous work on specific proteins of the granules, the neurophysins, will be extended in several ways. The possibility that neurophysins are present in the native state as lipoproteins will be investigated and, if confirmed, the nature and possible functions of these complexes will be studied. Of particular interest will be their role in transmembrane secretion. The hormone-binding and immunological properties of such complexes of neurophysins will be of particular interest. Soluble granule proteins other than neurophysins will also be investigated and intragranular proteolytic enzymes will be particularly searched for. The neurosecretory granule membrane will also be isolated and its composition studied to obtain evidence as to its functions. Neurosecretory granules will be isolated from porcine posterior pituitary tissue, primarily by density gradient centrifugation. The preparation will be examined by electron microscopy. Protein components will be characterized; of particular interest will be lipid content, electrophoretic behavior and amino acid composition, hormone-binding and enzymatic activity. Granule membranes will be studied by similar methods. BIBLIOGRAPHIC REFERENCE: Ting-chi Wuu and Sara E. Crumm. Characterization of Porcine Neurophysin-III: Its Resemblance and Possible Relationships to Porcine Neurophysin-I. J. Biol. Chem. (1976) 251, 2735-2739.